After its discovery in 1893 in Rhode Island, blackhead disease was reported across the continent and soon in many other countries. It decimated the turkey industry in New England and followed production like a faithful shadow. Blackhead disease causes high mortality in turkeys, sometimes approaching 100% of a flock. In chickens, the mortality may be 10%–20% with high morbidity, although many outbreaks pass unnoticed. Early workers identified Histomonas meleagridis, a protozoan related to Entamoeba histolytica, Giardia lamblia, and Trichomonas, as the causative agent. Like many other parasites, its life cycle is complex, involving as an intermediate host, the common cecal worm Heterakis gallinarum. The necessity for bacteria for Histomonas to become virulent in the turkey and chicken, notably Escherichia coli, Bacillus subtilis, and Clostridium spp., was discovered by research in gnotobiotic birds. Changes in management brought the disease under control, although it remained the first cause of mortality in turkeys until modern antihistomonal products were developed after WWII. The ban of nitroimidazole products in the United States and Europe was followed by an upsurge in reported cases in turkeys and chickens. Immunization is not an option for prevention, as birds do not reliably become resistant to reinfection after suffering a primary exposure. Recent research demonstrated that histomoniasis could spread rapidly through a flock of turkeys by direct contact, probably involving the phenomenon of cloacal drinking. Direct transmission was not demonstrated for chickens, stressing dependence on H. gallinarum as the source of infection. The lack of suitable treatment drugs or vaccines emphasizes the importance of prevention by worm control and management.